3 TB Vignettes

A 20-year-old woman, in her first trimester of pregnancy, presents to the ante-natal clinic (ANC) for routine care. After counseling she volunteered for HIV testing and was found to be HIV positive. She is now enrolled in the pregnancy HIV clinic for antenatal care specific to her needs.

On History
This is her first pregnancy; it was unplanned and occurred due to unprotected sexual intercourse. She has never used oral contraceptives nor has she practiced safe sex. This is her third partner this year.
She complains that she has lost 4kg in the past two months. During this time she has also had a persistent cough.

On examination

• Thin, but no signs of wasting.
• No lymphadenopathy
• Crackles in the upper lobe of the left lung.
• No other significant findings

FBC:

5.40 WCC  (4.00-10.00 x 109/L)
64% neutrophils; 33% lymphocytes.
Haemoglobin:  9.5 g/dl (12.1-16.3 g/dl)
CD4 count:  320 cells/mm³ (1000-1800 cells/mm³)
Sputum sample:  AFB positive

Discussion
The essential or firstline TB drugs are:
Isoniazid, Rifampicin, Ethambutol, Pyrazinamide and Streptomycin.

There are three main properties of TB drugs:

• bactericidal activity
• sterilising activity
• ability to prevent resistance

The essential (firstline) TB drugs have these properties in different proportions. Isoniazid and rifampicin are the most powerful bactericidal drugs, active against all populations of TB bacilli. Rifampicin is the most potent sterilising drug available. Pyrazinamide and streptomycin are also bactericidal against certain populations of TB bacilli. Pyrazinamide is only active in an acid environment. Streptomycin is bactericidal against rapidly multiplying TB bacilli. Ethambutol is used in association with more powerful drugs to prevent the emergence of resistant bacilli.

TB treatment
Essential or firstline treatment for a newly diagnosed patient is isoniazid, rifampicin, pyrizinamide, and ethambutol for two months (initial phase), then isoniazid and rifampicin alone for a further four months (continuation phase). The first two months of treatment is given with DOTS (directly observed treatment, short-course) which helps to improve adherence. Usually during the first two weeks tubercle bacilli are rapidly killed and infectious patients become non-infectious. During the continuation phase fewer drugs are needed but for a longer period. The sterilising effect of the drugs eliminates the remaining bacilli and prevents relapse.

At the end of the second month of treatment, most patients will have a negative sputum smear, however if a patient has a positive sputum smear at this time, this may indicate one of the following:

• most frequently, that the initial phase of therapy was poorly supervised and that patient adherence was poor;
• occasionally that there is a slow rate of progress with sputum smear conversion, e.g. if a patient had extensive cavitation and a heavy initial bacillary load;
• rarely, that the patient may have drug-resistant TB that does not respond to first-line treatment.

TB in pregnant women
Untreated tuberculosis (TB) represents a greater hazard to a pregnant woman and her foetus than the treatment does. The outcome of a pregnancy is not altered by TB drugs. Even though the drugs do cross the placenta they do not have harmful effects on the foetus. However, infants born to mothers with untreated TB are usually low birth weight babies and may be born with TB themselves. Therefore TB treatment of pregnant women should be initiated whenever the disease is present.

TB treatment in HIV positive pregnant women
In patients who have both TB and HIV, TB treatment takes priority over ARV therapy, and should never be compromised. If a patient is diagnosed with TB, they must be started immediately on treatment. Rather delay or replace the ARV therapy if there are drug interactions than delay the TB treatment. TB treatment with DOTS should be initiated immediately in a pregnant woman diagnosed with active TB, irrespective of whether she is on ARVs or not.

When TB infection is present before starting ARVs, consider the following:

• If CD4 count > 200 and patient is less then WHO stage IV disease – start TB treatment and asses the need for ARVs at completion of TB therapy using CD4 count and clinical criteria.
• If CD4 count < 200 and/or WHO stage IV disease present – delay ARVs until after 2 month of TB therapy
•  If CD4 count < 50 – introduce ARVs as soon as patient is stabilised on TB therapy ( typically 2 wks).
• If TB develops and patients are already on ARVs then continue ARVs throughout the TB treatment. The following changes should be made:

• 1st line ARV therapy change nevirapine to efavirenz
• 2nd line therapy lopinavir/ritonavir, increase the dosage of ritonavir to 400mg

Contraindicated treatments
Nevirapine and rifampicin should not be used together, because rifampicin is a potent inducer of liver enzymes and lowers the blood levels of nevirapine (Dose adjustments for co administration have not yet been established).
Nevirapine and rifampicin-based TB treatment should not be used together because of the potential hepatotoxicity. Efavirenz is contraindicated in pregnancy, especially during the first trimester, because of its potential for birth defects of the CNS. However, if there is no alternative drug available, efavirenz should only be used after the first trimester, and if it has to be used in the first trimester the mother must be counseled. Streptomycin is contraindicated in pregnancy because it is ototoxic to the foetus and can cause permanent deafness.

Plan for this patient:
Adherence counseling.
Begin ARVs after the first two months of TB treatment. Full dose HAART to include stavudine, lamivudine, nevirapine. If the therapy is used for at least 12 weeks before delivery and throughout the breast feeding it will reduce HIV transmission rates to the baby down to 1-2%.
When ARVs are started TB symptoms may transiently worsen as part of Immune Reconstitution Inflammatory Syndrome (IRIS).

Acknowledgement
This case study was kindly provided by Dr Monica Mercer from Immunopaedia